The natural history of acute colitis (AC), chronic mucosal changes (CMC) and adenocarcinoma of the colon (CA) was determined in 212 cotton-top tamarins from birth up to 5 years of age from a total of 2790 biopsies of the distal colon taken every 4 months or from necropsy specimens of the entire colon. Twin animals were raised from birth in two environments one in a breeding colony where colitis was endemic and the other in an isolation unit. They were fed one of three different diets a standard tamarin diet; a semipurified high-fat low-fiber diet or a high-fiber low-fat diet. AC and CMC were characterized as a disease that started in infancy, responded to treatment but recurred at varying intervals. The most striking finding was a significantly higher incidence of AC and CMC in animals raised in the colony compared to those in the isolation unit. Regardless of environment, the incidence of CMC was higher among animals fed a standard diet than either of the semipurified diets. Seven cases of CA developed among animals over 4 years of age 6/20 (30.0%) were fed a standard diet and were raised in the colony; 1/4 was fed a standard diet and was raised in isolation. The prevalence of AC and CMC was significantly higher among animals with cancer than among their twins or siblings who did not develop cancer. This study suggests that AC and CMC in the tamarin were associated with a transmissible agent and that diet may modify the CMC but had no effect on AC.